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The Impact of Primary Treatment Strategy on the Quality of Life in Patients with Vestibular Schwannoma
Accepted Manuscript The Impact Of Primary Treatment Strategy On Vestibular Schwannoma Patient Quality Of Life Robert W. Foley, Robert M. Maweni, Hussein Jaafar, Rory McConn Walsh, Mohsen Javadpour, Daniel Rawluk PII:
S1878-8750(17)30260-7
DOI:
10.1016/j.wneu.2017.02.087
Reference:
WNEU 5318
To appear in:
World Neurosurgery
Received Date: 2 October 2016 Revised Date:
16 February 2017
Accepted Date: 17 February 2017
Please cite this article as: Foley RW, Maweni RM, Jaafar H, McConn Walsh R, Javadpour M, Rawluk D, The Impact Of Primary Treatment Strategy On Vestibular Schwannoma Patient Quality Of Life, World Neurosurgery (2017), doi: 10.1016/j.wneu.2017.02.087. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT The Impact Of Primary Treatment Strategy On Vestibular Schwannoma Patient Quality Of Life
Robert W Foley1,2, Robert M Maweni3, Hussein Jaafar4, Rory McConn Walsh5, Mohsen
(1) UCD School of Medicine, University College Dublin, Ireland.
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Javadpour6, Daniel Rawluk6.
(2) UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Ireland.
(3) Croydon University Hospital, Croydon NHS Trust, London, United Kingdom.
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(4) Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom.
(5) Department of Otolaryngology, Beaumont Hospital, Dublin, Ireland.
Corresponding Author:
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(6) Department of Neurosurgery, Beaumont Hospital, Dublin, Ireland.
Robert Foley, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
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Email: [email protected]
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Conflict of Interest: The authors declare that they have no conflict of interest.
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Running Title: Vestibular Schwannoma Quality of Life
Keywords: Vestibular Schwannoma; Quality of Life; Microsurgery, Stereotactic Radiosurgery; Observation; Questionnaire;
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Abstract
Objective: To assess the quality of life (QoL) in a representative sample of vestibular schwannoma patients and to ascertain the differences in outcomes associated with
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distinct management strategies.
Patients & Methods: Vestibular Schwannoma patients attending a tertiary referral centre were asked to complete the FACT-Br Questionnaire, which assesses QoL in five domains: physical, social, emotional and functional and a brain cancer specific domain.
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Results were analysed in the overall cohort and in surgery, stereotactic radiosurgery and conservative management subgroups. The relationship between patient clinical
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characteristics and QoL outcome was also analysed by univariable and multivariable logistic regression.
Results: There were 83 survey respondents with an average age of participants of 57 years and a mean follow up of 4.9 years. QoL was statistically significantly lower in the surgery subgroup within the Physical QoL domain (p=0.039). However there was no
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significant difference in overall QoL between the three subgroups of surgery, radiosurgery and conservative management (p=0.17). A poor QoL outcome was associated with the number of symptoms at diagnosis, greater tumour size and a
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surgical management strategy.
Conclusions: The QoL within this patient cohort was extremely variable in each management group, mirroring the heterogeneous natural history of this disease process.
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QoL in vestibular schwannoma patients cannot be predicted based on management strategy alone but a poor QoL outcome is more likely in patients with larger, symptomatic tumours that are surgically treated.
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Introduction Vestibular schwannoma (VS), or acoustic neuroma, refers to a benign tumour of the Schwann cell arising from the VIIIth cranial nerve 1. They account for 6% of all intracranial tumours 2 and have an incidence of approximately 1.2 per 100,000 3. There are three main treatment options for VS: Microsurgical resection, Stereotactic 3,4.
Currently, the
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Radiosurgery, and a conservative approach with serial imaging
decision regarding management is based on patient factors such as age, functional status, symptoms at presentation and patient preference as well as tumour specific factors namely size, location & growth velocity
3,5.
However, there are a lack of
that such a study would be performed.
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randomised control trials comparing the treatment approaches for VS 6 and it is unlikely
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Efforts must be made to find other sources of meaningful comparison and quality of life (QoL) outcomes represent one such source. In view of the management options we set out to identify the impact of the diagnosis and subsequent management of the subgroups of patients within our practice. Most patients present with sensorineural hearing loss or tinnitus and because VS is a benign disease with troublesome symptoms, which may not improve with intervention 5, it has the potential to cause a profound
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impact on the psychosocial well being of the patient. Patient self-reported QoL has thus become a large area of interest within the literature. VS patients, in particular those treated with microsurgery, have been demonstrated to have lower QoL scores
7–10
and
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lower emotional intelligence scores 11 in comparison to age and sex-matched controls.
QoL is defined by the World Health Organisation as "an individual's' perception of their
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position in life...affected in a complex way by the person's' physical health, psychological state, level of independence, social relationships and their relationship to salient features of their environment”
12.
This is increasingly important because chronic
illnesses, such as VS, are associated with comorbid mental health illnesses -with depression and anxiety states the most commonly described
13,14.
Providing one’s
patients with accurate, evidence based information regarding QOL outcomes following a diagnosis of VS is an important step towards personalised medicine and can allow for an informed decision regarding treatment on an individual basis. This is particularly important in cases of small tumours, where patient preferences may dictate management 4. Indeed, with the evolving paradigm of VS management moving towards a
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ACCEPTED MANUSCRIPT more conservative approach to treatment, the results of studies regarding QoL outcomes take on greater significance.
Thus, we sought to assess the psychosocial impact of a VS diagnosis and to ascertain which treatment strategy offers patients the best QoL outcome. Furthermore we sought
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Materials & Methods
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to study which patient characteristics are associated with poor QoL.
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The present study is an anonymous cross-sectional questionnaire based cohort design. Ninety-five patients with vestibular schwannoma attending the Skull-Base clinic between September 2014 and June 2015 with variable lengths of follow-up were asked to complete the ‘Functional Assessment of Chronic Illness Therapy-Brain’ (FACT-Br) questionnaire in the outpatient centre prior to their appointment. Written informed consent was obtained from all the study participants and this study received ethical
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approval from our institutional Hospital Ethics Committee Board. Permission to use this tool for the present study was acquired from the FACIT organisation. A total of 83 patients out of the 95 individuals were surveyed giving a response rate of 87%. 10 patients declined to participate, one patient had to stop due to reading difficulties and
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one patient withdrew consent following an emotional reaction to the survey contents. Patients with Neurofibromatosis type 2, comorbid psychiatric conditions or those with a
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new diagnosis (<6 months) were excluded from the study.
The FACT-Br is a 50 item questionnaire (see supplementary material) which allows for a multidimensional assessment of QoL and is easy to administer
15.
The FACT-Br
questionnaire assesses QoL measures in terms of health related quality of life rather than just health function, and has domains to assess for physical, social/family, emotional, functional and general wellbeing 16. Thus, it is a combination of the two most common approaches to QoL assessment with the opportunity to assess core QoL measures as well as disease specific QoL components 16. The questionnaire is based on Likert scale questions and was analysed according to the FACT-Br instructions to ascertain scores for each QoL domain and overall QoL. Results were analysed in the
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ACCEPTED MANUSCRIPT overall cohort and in microsurgery, radiosurgery and conservative management subgroups. A subgroup analysis was also performed in those patients with smaller tumours (<2.5cm). Differences between each QoL domain in patient subgroups were analysed using the one-way AVONA test. Sample size estimation using a 95% confidence interval, 90% power, and a standard deviation of .5 estimated an adequate sample size
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of 86.
In order to analyse those patients with good versus poor QoL outcomes, the total score on the FACT-Br was dichotomised with those falling below the median value defined as having a ‘poor QoL outcome’ and those above the median value a ‘good QoL outcome’.
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The minimal clinically significant difference published for the FACT-general is between 3 and 7. Therefore those patients with a total FACT-Br score, which fell within the minimal clinically significant difference were excluded from the logistic regression
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analysis. The relationship between patient clinical characteristics and QoL outcome was analysed by univariable and multivariable logistic regression. Odds Ratios and 95% confidence intervals were calculated and a p value of <0.05 is considered statistically
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significant. Statistical analysis was carried using R software v0.98 [14].
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Results
The study cohort characteristics are summarised in Table 1. Eighty-three patients completed the questionnaire and the primary treatment strategy was conservative
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management in 59% of patients, surgery in 24% and radiosurgery in 17%. The mean ages of the patient subgroups were 60 years, 51 years and 55 years respectively. The average follow-up time since diagnosis was 4.9 years. 66% of patients were women and the majority of patients had tumours measuring <1.5 cm. No patients reported membership of a VS-specific support group, and only 3 patients were members were members of a support group of any kind. 76% of the overall patient cohort was able to resume their usual occupation following their diagnosis; 86% in the conservatively managed, 78% in the radiosurgery subgroup and 50% of those treated with microsurgery (p= 0.006).
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ACCEPTED MANUSCRIPT The results of the FACT-Br are shown in full in Table 2 and are illustrated in the form of a radar chart in Figure 1.
Between the subgroups of conservative, surgery and
radiosurgery treatment strategies there was no difference in overall QoL scores (p=0.17). There was also no significant difference in QoL scores within the Social/Family domain (p=0.42), the Emotional domain (p=0.54), the Functional domain (p=0.45) or the general QoL domain (p=0.18). However, those patients in the surgery treatment
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group reported significantly lower QoL scores compared to both conservative management and radiosurgery within the Physical domain (p=0.005). However, in our subgroup analysis of patients with VS less than 2.5cm in size there were no differences in overall QoL (p=0.17), Social/Family (p=0.43), Emotional (p=0.08), Functional
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(p=0.60), Physical (p= 0.43) or general QoL domains (p=0.45).
Table 3 summarises the results of univariable and multivariable analysis, which
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demonstrates the relationship between a poor QoL outcome and patient’s clinical characteristics. On univariate analysis a poor QoL outcome was associated the following patient characteristics, namely, tumour size >2.5cm (OR: 1.35; 95% CI, 0.38 – 4.37), a surgical management strategy (OR: 1.37; 95% CI, 0.27 - 6.79) and male sex (OR: 1.65; 95% CI, 0.57 - 4.76). These risk factors for a poor QoL, however, did not demonstrate statistical significance (p>0.05). On multivariable analysis, a poor QoL outcome was
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associated with tumour size >2.5cm (OR: 1.25; 95% CI, 0.07 – 1.82; p=0.87), surgical management (OR: 2.12; 95% CI, 1.18 – 38.0; p=0.59) and symptoms at diagnosis (OR:
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1.68; 95% CI, 0.99 - 3.18; p=0.07).
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Discussion Our findings demonstrate that the treatment strategy selected for VS patients significantly affects QOL outcomes within the physical domain, however when analysing only those patients with tumours <2.5cm there were no differences in QoL outcomes. A
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2004 study from Sandooram et al. examined QoL life following microsurgery, radiosurgery and conservative management and found no statistically significant difference in QoL scores amongst these patient subgroups 17. There was a deterioration in QoL amongst those treated with microsurgery and radiosurgery however this did not reach statistical significance. Interestingly, there was no difference in physical QoL
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between treatment subgroups and furthermore the data regarding QOL ranged greatly from positive to negative scores. This heterogeneity of QoL scores is mirrored in the
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present study. A second study from Sandooram et al. evaluated these three treatment subgroups prospectively and again found no statistically significant differences in QoL 18.
Furthermore, Di Maio et al. demonstrated that there were no differences in QoL
outcomes based on treatment strategy over a follow-up period of 24 months 19. Finally, Brooker et al. found no statistically significant discrepancies in patient self-reported QoL
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scores in a study of 180 patients 20.
In contrast to the above studies, Carlson et al. found some differences in QoL life scores within their microsurgical patient cohort from a study of 576 patients 21. The majority of QoL measures demonstrated no significant differences however; patients with
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microsurgical treatment reported lower facial, balance and pain scores on the Penn Acoustic Neuroma Quality-of-Life tool. However, it is noteworthy that the differences between patients with VS and patients without VS (controls) were greater than the
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differences between VS subgroups. This suggests that it is the diagnosis of VS that most impacts QoL and not the treatment strategy selected.
A number of studies examine differences in QoL outcomes between treatment groups, but many of these fail to address the three strands of treatment. For example, Myrseth et al. concluded that radiosurgery was more favoured than microsurgery based on superior QoL scores as well as superior post-treatment facial nerve function, hearing and complication rates
22.
Myrseth and colleagues later conducted a prospective study
and this demonstrated that QoL was significantly better in patients treated with radiosurgery compared to microsurgery 6. While Breivik et al. showed no difference in quality of life outcome amongst patients treated with radiosurgery and those managed
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ACCEPTED MANUSCRIPT conservatively, with a mean follow-up time of 55 months
23.
A 2015 paper by Kim and
colleagues performs a subgroup analysis of conservative, radiosurgery and surgery
24,
and demonstrated significant differences between subgroups in a number of QoL domains. These results further emphasise that QoL can be highly variable in distinct patient cohorts and should be assessed in each individual patient.
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Jufas et al. have shown that surgically treated patients had lower scores within their physical and social functioning 25. While Cheng et al. demonstrated in a study of QoL in post-surgery VS patients that only one health domain; that of physical limitation, was significantly impacted upon compared to healthy controls 7,26,27.
and this result has been
Factors such as tumour size, age, gender and surgical
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replicated in other studies
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approach proved inconsequential to patients QOL outcomes. These results are similar to the present study, in which QoL was significantly lower in the surgically treated
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subgroup within the physical QoL domain. We also did not find statistically significant associations between QoL outcomes and a number of basic clinical characteristics, however poor QoL did have a relationship with larger tumours, a surgical treatment strategy and symptoms at diagnosis. There were no differences in any of the QoL domains when analysing the patient subgroup with tumours <2.5cm in size. Analysis of this subgroup is especially important because these patients represent those in whom it
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would be reasonable to select any of the three management strategies. Our findings support those of Carlson et al., who also demonstrated that QoL in VS patients was not influenced by gender, age or treatment strategy 28. In this study a total of 538 patients were surveyed and the authors conclude that QoL outcome is most impacted upon by
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the severity of one’s symptoms, in particular that of headache and dizziness, and this
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study focused their analysis on patients with VS sizes of less than 3 cm.
The impact of biopsychosocial factors such as involvement in a patient support group and post-diagnosis occupational function were also explored. Very few patients were members of a support group within this study cohort. This could provide an avenue for potential intervention and may represent a strategy to improve VS patient QoL. One patient provided us with a qualitative piece of information, stating that the support groups currently available in Ireland do not tailor to her needs as most patients are suffering from more aggressive primary brain neoplasms. We however, did not explore the use of Internet based support groups or forums and there is a possibility that patients are using this mechanism for psychological support. Furthermore, patients returning to their previous occupation were significantly decreased in the surgically
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ACCEPTED MANUSCRIPT treated patient group and this is concordant with the lower physical QoL scores. The reduction in the return to work of patients undergoing surgery in this study warrants further investigation. Inability to return to work has the potential to considerably impact one’s sense of self and perhaps this impact has not been fully captured through the use of this questionnaire.
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We recognise a number of limitations to this study. The pragmatic design, in which patients attending their outpatient were asked to complete a questionnaire, raises some potential biases. There may be a reporting bias, secondary to patients being worried about their upcoming appointment; imaging results, the possibility of surgery etc. Non-
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response bias is also an inherent bias of all questionnaire-based studies, which we have attempted to avoid through our study design. Our use of the outpatient department allowed us to achieve a relatively high response rate, however it may have caused a
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selection bias. One limitation of this study is that the surgical patients had operations spanning a large number of years. With contemporary management strategies, the degree of physical disability may be decreased, due to facial nerve preservation and SRS for residual tumour becoming the new standard of care. In the study of Vestibular schwannoma, as a rare disease, it is difficult to accrue a large numbers of patients and therefore one must draw conclusions from the univariable and mutivariable regression
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analysis with caution. The authors of the present study chose to assess patient QoL using the Fact-Br questionnaire rather than the commonly used short form 36 health survey (SF-36) or the relatively novel 26 item PANQOL tool. The SF-36 is a tool for assessing QoL in a number of areas important to all patients whereas the PANQOL tool was
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created to focus on those patients with Acoustic Neuroma only
8,29.
Although
comparisons between studies are made more difficult through the use of diverse tools,
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the Fact-Br was chosen, as we believed it provided a reliable method of QoL assessment that was more comprehensive than those offered by other aforementioned tools. In the clinical setting, patients will decide upon the best treatment strategy for them, based on the information provided to them by their surgeon. This study offers additional results that can be used to facilitate treatment decisions in a patient-centred approach to clinical decision-making. There was a wide variation in QoL score throughout this cohort with scores ranging from as low as 98 to as high as 200. Because no clinical characteristics were found to be predictive of a patient’s QoL score, we would recommend a proactive approach towards QoL assessment in one’s VS patients.
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Conclusion The diagnosis of vestibular schwannoma has the potential to cause a substantial impact upon each patient’s quality of life and the present study demonstrates that this impact can occur regardless of the treatment strategy selected. The quality of life within this patient cohort was extremely variable in each management group, mirroring the
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heterogeneous natural history of this disease process. There was no difference in overall quality of life; however, those patients treated with microsurgery had significantly lower
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scores within the physical domain and were less likely to return to work.
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Figure 1
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Figure Legends
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Radar chart illustrating QoL scores in each domain as assessed by the FACT-Br. Values in each QoL domain are expressed as percentages of the total QoL score that could be achieved and the scale of the axis in each domain ranges from 60-100%. There are higher scores for the conservatively treated patients in the majority of QoL domains, however the surgery and radiosurgery cohorts have higher emotional and social QoL scores.
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Table 1 – Clinical Characteristics of the patient cohort
Mean Time Since Diagnosis (years)
57.2 (20-83) 24 (29%) 22 (27%) 20 (24%) 17 (20%)
60.3 (30-83) 12 (25%) 10 (20%) 15 (31%) 12 (24%)
4.9
55 (66%) 28 (34%)
Tumour Size (cm) <1.5 1.5-2.4 2.5-3.4 3.5-4.4 ≥4.5
41 (49%) 21 (25%) 7 (9%) 4 (5%) 9 (11%)
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Gender Female Male
Surgery
Radiotherapy
20 (24%)
14 (17%)
51.3 (20-70) 8 (40%) 6 (30%) 3 (15%) 3 (15%)
54.9 (35-73) 4 (29%) 6 (43%) 2 (14%) 2 (14%)
4.5
4.8
6.42
33 (67%) 16 (33%)
12 (60%) 8 (40%)
10 (71%) 4 (29%)
0 (0%) 4 (20%) 6 (30%) 2 (10%) 8 (40%)
5 (36%) 6 (43%) 1 (7%) 1 (7%) 1 (7%)
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49 (59%)
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Conservative
83
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Mean Age (range) <50 50-59 60-69 70+
All
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Patients (%)
36 (73%) 12 (24%) 0 (0%) 1 (2%) 0 (0%)
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Table 2 – Average QoL Scores Separated By Domain
Conservative
Surgery
Radiotherapy
p value†
Physical (0-28)
22.34
23.95
19.36
20.83
0.005
Social/Family (0-28)
23.94
24.57
23.07
22.99
0.42
Emotional (0-24)
17.22
17.40
16.14
18.21
0.54
Functional (0-28)
21.12
21.83
19.72
20.79
0.45
Brain Tumour Subscale Score (0-92)
68.83
70.80
65.51
66.97
0.35
General QoL Score (0-108)
84.75
87.50
79.85
82.46
0.18
Total (0-200)
153.35
158.29
144.64
148.76
0.17
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One Way ANOVA. QoL = Quality of Life.
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†
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All
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Table 3 – Odds Ratios and 95% Confidence Intervals for the association of various patient characteristics and a poor QoL outcome
1.35 1.37 1.65 1.02
(0.38-4.37) (0.27-6.79) (0.57-4.76) (0.78-1.34)
p value 0.64 0.69 0.34 0.86
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Size >2.5cm Surgical Management¥ Male Symptoms at Diagnosis* ¥
Multivariate Analysis‡ Odds Ratio (95% CI) p value
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Univariate Analysis Odds Ratio (95% CI)
1.25 2.12 1.00 1.68
(0.07-1.82) (0.12-38.0) (0.25-3.97) (0.99-3.18)
0.87 0.59 0.99 0.07
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Serial imaging as primary management strategy without surgical or radiotherapy intervention * Number of symptoms at the time of diagnosis as a result of one’s vestibular schwannoma ‡ Multivariate Analysis also controlling for age at diagnosis, age at time of the present study, treatment strategy, years since diagnosis, symptoms at time of the present study and number of comorbidities
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ACCEPTED MANUSCRIPT VS: Vestibular Schwannoma QoL: Quality of Life
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FACT-Br: Functional Assessment of Chronic Illness Therapy-Brain
S1878-8750(17)30260-7
DOI:
10.1016/j.wneu.2017.02.087
Reference:
WNEU 5318
To appear in:
World Neurosurgery
Received Date: 2 October 2016 Revised Date:
16 February 2017
Accepted Date: 17 February 2017
Please cite this article as: Foley RW, Maweni RM, Jaafar H, McConn Walsh R, Javadpour M, Rawluk D, The Impact Of Primary Treatment Strategy On Vestibular Schwannoma Patient Quality Of Life, World Neurosurgery (2017), doi: 10.1016/j.wneu.2017.02.087. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT The Impact Of Primary Treatment Strategy On Vestibular Schwannoma Patient Quality Of Life
Robert W Foley1,2, Robert M Maweni3, Hussein Jaafar4, Rory McConn Walsh5, Mohsen
(1) UCD School of Medicine, University College Dublin, Ireland.
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Javadpour6, Daniel Rawluk6.
(2) UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Ireland.
(3) Croydon University Hospital, Croydon NHS Trust, London, United Kingdom.
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(4) Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom.
(5) Department of Otolaryngology, Beaumont Hospital, Dublin, Ireland.
Corresponding Author:
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(6) Department of Neurosurgery, Beaumont Hospital, Dublin, Ireland.
Robert Foley, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
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Email: [email protected]
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Conflict of Interest: The authors declare that they have no conflict of interest.
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Running Title: Vestibular Schwannoma Quality of Life
Keywords: Vestibular Schwannoma; Quality of Life; Microsurgery, Stereotactic Radiosurgery; Observation; Questionnaire;
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Abstract
Objective: To assess the quality of life (QoL) in a representative sample of vestibular schwannoma patients and to ascertain the differences in outcomes associated with
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distinct management strategies.
Patients & Methods: Vestibular Schwannoma patients attending a tertiary referral centre were asked to complete the FACT-Br Questionnaire, which assesses QoL in five domains: physical, social, emotional and functional and a brain cancer specific domain.
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Results were analysed in the overall cohort and in surgery, stereotactic radiosurgery and conservative management subgroups. The relationship between patient clinical
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characteristics and QoL outcome was also analysed by univariable and multivariable logistic regression.
Results: There were 83 survey respondents with an average age of participants of 57 years and a mean follow up of 4.9 years. QoL was statistically significantly lower in the surgery subgroup within the Physical QoL domain (p=0.039). However there was no
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significant difference in overall QoL between the three subgroups of surgery, radiosurgery and conservative management (p=0.17). A poor QoL outcome was associated with the number of symptoms at diagnosis, greater tumour size and a
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surgical management strategy.
Conclusions: The QoL within this patient cohort was extremely variable in each management group, mirroring the heterogeneous natural history of this disease process.
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QoL in vestibular schwannoma patients cannot be predicted based on management strategy alone but a poor QoL outcome is more likely in patients with larger, symptomatic tumours that are surgically treated.
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Introduction Vestibular schwannoma (VS), or acoustic neuroma, refers to a benign tumour of the Schwann cell arising from the VIIIth cranial nerve 1. They account for 6% of all intracranial tumours 2 and have an incidence of approximately 1.2 per 100,000 3. There are three main treatment options for VS: Microsurgical resection, Stereotactic 3,4.
Currently, the
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Radiosurgery, and a conservative approach with serial imaging
decision regarding management is based on patient factors such as age, functional status, symptoms at presentation and patient preference as well as tumour specific factors namely size, location & growth velocity
3,5.
However, there are a lack of
that such a study would be performed.
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randomised control trials comparing the treatment approaches for VS 6 and it is unlikely
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Efforts must be made to find other sources of meaningful comparison and quality of life (QoL) outcomes represent one such source. In view of the management options we set out to identify the impact of the diagnosis and subsequent management of the subgroups of patients within our practice. Most patients present with sensorineural hearing loss or tinnitus and because VS is a benign disease with troublesome symptoms, which may not improve with intervention 5, it has the potential to cause a profound
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impact on the psychosocial well being of the patient. Patient self-reported QoL has thus become a large area of interest within the literature. VS patients, in particular those treated with microsurgery, have been demonstrated to have lower QoL scores
7–10
and
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lower emotional intelligence scores 11 in comparison to age and sex-matched controls.
QoL is defined by the World Health Organisation as "an individual's' perception of their
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position in life...affected in a complex way by the person's' physical health, psychological state, level of independence, social relationships and their relationship to salient features of their environment”
12.
This is increasingly important because chronic
illnesses, such as VS, are associated with comorbid mental health illnesses -with depression and anxiety states the most commonly described
13,14.
Providing one’s
patients with accurate, evidence based information regarding QOL outcomes following a diagnosis of VS is an important step towards personalised medicine and can allow for an informed decision regarding treatment on an individual basis. This is particularly important in cases of small tumours, where patient preferences may dictate management 4. Indeed, with the evolving paradigm of VS management moving towards a
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ACCEPTED MANUSCRIPT more conservative approach to treatment, the results of studies regarding QoL outcomes take on greater significance.
Thus, we sought to assess the psychosocial impact of a VS diagnosis and to ascertain which treatment strategy offers patients the best QoL outcome. Furthermore we sought
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Materials & Methods
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to study which patient characteristics are associated with poor QoL.
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The present study is an anonymous cross-sectional questionnaire based cohort design. Ninety-five patients with vestibular schwannoma attending the Skull-Base clinic between September 2014 and June 2015 with variable lengths of follow-up were asked to complete the ‘Functional Assessment of Chronic Illness Therapy-Brain’ (FACT-Br) questionnaire in the outpatient centre prior to their appointment. Written informed consent was obtained from all the study participants and this study received ethical
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approval from our institutional Hospital Ethics Committee Board. Permission to use this tool for the present study was acquired from the FACIT organisation. A total of 83 patients out of the 95 individuals were surveyed giving a response rate of 87%. 10 patients declined to participate, one patient had to stop due to reading difficulties and
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one patient withdrew consent following an emotional reaction to the survey contents. Patients with Neurofibromatosis type 2, comorbid psychiatric conditions or those with a
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new diagnosis (<6 months) were excluded from the study.
The FACT-Br is a 50 item questionnaire (see supplementary material) which allows for a multidimensional assessment of QoL and is easy to administer
15.
The FACT-Br
questionnaire assesses QoL measures in terms of health related quality of life rather than just health function, and has domains to assess for physical, social/family, emotional, functional and general wellbeing 16. Thus, it is a combination of the two most common approaches to QoL assessment with the opportunity to assess core QoL measures as well as disease specific QoL components 16. The questionnaire is based on Likert scale questions and was analysed according to the FACT-Br instructions to ascertain scores for each QoL domain and overall QoL. Results were analysed in the
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ACCEPTED MANUSCRIPT overall cohort and in microsurgery, radiosurgery and conservative management subgroups. A subgroup analysis was also performed in those patients with smaller tumours (<2.5cm). Differences between each QoL domain in patient subgroups were analysed using the one-way AVONA test. Sample size estimation using a 95% confidence interval, 90% power, and a standard deviation of .5 estimated an adequate sample size
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of 86.
In order to analyse those patients with good versus poor QoL outcomes, the total score on the FACT-Br was dichotomised with those falling below the median value defined as having a ‘poor QoL outcome’ and those above the median value a ‘good QoL outcome’.
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The minimal clinically significant difference published for the FACT-general is between 3 and 7. Therefore those patients with a total FACT-Br score, which fell within the minimal clinically significant difference were excluded from the logistic regression
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analysis. The relationship between patient clinical characteristics and QoL outcome was analysed by univariable and multivariable logistic regression. Odds Ratios and 95% confidence intervals were calculated and a p value of <0.05 is considered statistically
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significant. Statistical analysis was carried using R software v0.98 [14].
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Results
The study cohort characteristics are summarised in Table 1. Eighty-three patients completed the questionnaire and the primary treatment strategy was conservative
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management in 59% of patients, surgery in 24% and radiosurgery in 17%. The mean ages of the patient subgroups were 60 years, 51 years and 55 years respectively. The average follow-up time since diagnosis was 4.9 years. 66% of patients were women and the majority of patients had tumours measuring <1.5 cm. No patients reported membership of a VS-specific support group, and only 3 patients were members were members of a support group of any kind. 76% of the overall patient cohort was able to resume their usual occupation following their diagnosis; 86% in the conservatively managed, 78% in the radiosurgery subgroup and 50% of those treated with microsurgery (p= 0.006).
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ACCEPTED MANUSCRIPT The results of the FACT-Br are shown in full in Table 2 and are illustrated in the form of a radar chart in Figure 1.
Between the subgroups of conservative, surgery and
radiosurgery treatment strategies there was no difference in overall QoL scores (p=0.17). There was also no significant difference in QoL scores within the Social/Family domain (p=0.42), the Emotional domain (p=0.54), the Functional domain (p=0.45) or the general QoL domain (p=0.18). However, those patients in the surgery treatment
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group reported significantly lower QoL scores compared to both conservative management and radiosurgery within the Physical domain (p=0.005). However, in our subgroup analysis of patients with VS less than 2.5cm in size there were no differences in overall QoL (p=0.17), Social/Family (p=0.43), Emotional (p=0.08), Functional
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(p=0.60), Physical (p= 0.43) or general QoL domains (p=0.45).
Table 3 summarises the results of univariable and multivariable analysis, which
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demonstrates the relationship between a poor QoL outcome and patient’s clinical characteristics. On univariate analysis a poor QoL outcome was associated the following patient characteristics, namely, tumour size >2.5cm (OR: 1.35; 95% CI, 0.38 – 4.37), a surgical management strategy (OR: 1.37; 95% CI, 0.27 - 6.79) and male sex (OR: 1.65; 95% CI, 0.57 - 4.76). These risk factors for a poor QoL, however, did not demonstrate statistical significance (p>0.05). On multivariable analysis, a poor QoL outcome was
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associated with tumour size >2.5cm (OR: 1.25; 95% CI, 0.07 – 1.82; p=0.87), surgical management (OR: 2.12; 95% CI, 1.18 – 38.0; p=0.59) and symptoms at diagnosis (OR:
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1.68; 95% CI, 0.99 - 3.18; p=0.07).
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Discussion Our findings demonstrate that the treatment strategy selected for VS patients significantly affects QOL outcomes within the physical domain, however when analysing only those patients with tumours <2.5cm there were no differences in QoL outcomes. A
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2004 study from Sandooram et al. examined QoL life following microsurgery, radiosurgery and conservative management and found no statistically significant difference in QoL scores amongst these patient subgroups 17. There was a deterioration in QoL amongst those treated with microsurgery and radiosurgery however this did not reach statistical significance. Interestingly, there was no difference in physical QoL
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between treatment subgroups and furthermore the data regarding QOL ranged greatly from positive to negative scores. This heterogeneity of QoL scores is mirrored in the
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present study. A second study from Sandooram et al. evaluated these three treatment subgroups prospectively and again found no statistically significant differences in QoL 18.
Furthermore, Di Maio et al. demonstrated that there were no differences in QoL
outcomes based on treatment strategy over a follow-up period of 24 months 19. Finally, Brooker et al. found no statistically significant discrepancies in patient self-reported QoL
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scores in a study of 180 patients 20.
In contrast to the above studies, Carlson et al. found some differences in QoL life scores within their microsurgical patient cohort from a study of 576 patients 21. The majority of QoL measures demonstrated no significant differences however; patients with
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microsurgical treatment reported lower facial, balance and pain scores on the Penn Acoustic Neuroma Quality-of-Life tool. However, it is noteworthy that the differences between patients with VS and patients without VS (controls) were greater than the
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differences between VS subgroups. This suggests that it is the diagnosis of VS that most impacts QoL and not the treatment strategy selected.
A number of studies examine differences in QoL outcomes between treatment groups, but many of these fail to address the three strands of treatment. For example, Myrseth et al. concluded that radiosurgery was more favoured than microsurgery based on superior QoL scores as well as superior post-treatment facial nerve function, hearing and complication rates
22.
Myrseth and colleagues later conducted a prospective study
and this demonstrated that QoL was significantly better in patients treated with radiosurgery compared to microsurgery 6. While Breivik et al. showed no difference in quality of life outcome amongst patients treated with radiosurgery and those managed
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ACCEPTED MANUSCRIPT conservatively, with a mean follow-up time of 55 months
23.
A 2015 paper by Kim and
colleagues performs a subgroup analysis of conservative, radiosurgery and surgery
24,
and demonstrated significant differences between subgroups in a number of QoL domains. These results further emphasise that QoL can be highly variable in distinct patient cohorts and should be assessed in each individual patient.
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Jufas et al. have shown that surgically treated patients had lower scores within their physical and social functioning 25. While Cheng et al. demonstrated in a study of QoL in post-surgery VS patients that only one health domain; that of physical limitation, was significantly impacted upon compared to healthy controls 7,26,27.
and this result has been
Factors such as tumour size, age, gender and surgical
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replicated in other studies
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approach proved inconsequential to patients QOL outcomes. These results are similar to the present study, in which QoL was significantly lower in the surgically treated
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subgroup within the physical QoL domain. We also did not find statistically significant associations between QoL outcomes and a number of basic clinical characteristics, however poor QoL did have a relationship with larger tumours, a surgical treatment strategy and symptoms at diagnosis. There were no differences in any of the QoL domains when analysing the patient subgroup with tumours <2.5cm in size. Analysis of this subgroup is especially important because these patients represent those in whom it
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would be reasonable to select any of the three management strategies. Our findings support those of Carlson et al., who also demonstrated that QoL in VS patients was not influenced by gender, age or treatment strategy 28. In this study a total of 538 patients were surveyed and the authors conclude that QoL outcome is most impacted upon by
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the severity of one’s symptoms, in particular that of headache and dizziness, and this
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study focused their analysis on patients with VS sizes of less than 3 cm.
The impact of biopsychosocial factors such as involvement in a patient support group and post-diagnosis occupational function were also explored. Very few patients were members of a support group within this study cohort. This could provide an avenue for potential intervention and may represent a strategy to improve VS patient QoL. One patient provided us with a qualitative piece of information, stating that the support groups currently available in Ireland do not tailor to her needs as most patients are suffering from more aggressive primary brain neoplasms. We however, did not explore the use of Internet based support groups or forums and there is a possibility that patients are using this mechanism for psychological support. Furthermore, patients returning to their previous occupation were significantly decreased in the surgically
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ACCEPTED MANUSCRIPT treated patient group and this is concordant with the lower physical QoL scores. The reduction in the return to work of patients undergoing surgery in this study warrants further investigation. Inability to return to work has the potential to considerably impact one’s sense of self and perhaps this impact has not been fully captured through the use of this questionnaire.
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We recognise a number of limitations to this study. The pragmatic design, in which patients attending their outpatient were asked to complete a questionnaire, raises some potential biases. There may be a reporting bias, secondary to patients being worried about their upcoming appointment; imaging results, the possibility of surgery etc. Non-
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response bias is also an inherent bias of all questionnaire-based studies, which we have attempted to avoid through our study design. Our use of the outpatient department allowed us to achieve a relatively high response rate, however it may have caused a
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selection bias. One limitation of this study is that the surgical patients had operations spanning a large number of years. With contemporary management strategies, the degree of physical disability may be decreased, due to facial nerve preservation and SRS for residual tumour becoming the new standard of care. In the study of Vestibular schwannoma, as a rare disease, it is difficult to accrue a large numbers of patients and therefore one must draw conclusions from the univariable and mutivariable regression
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analysis with caution. The authors of the present study chose to assess patient QoL using the Fact-Br questionnaire rather than the commonly used short form 36 health survey (SF-36) or the relatively novel 26 item PANQOL tool. The SF-36 is a tool for assessing QoL in a number of areas important to all patients whereas the PANQOL tool was
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created to focus on those patients with Acoustic Neuroma only
8,29.
Although
comparisons between studies are made more difficult through the use of diverse tools,
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the Fact-Br was chosen, as we believed it provided a reliable method of QoL assessment that was more comprehensive than those offered by other aforementioned tools. In the clinical setting, patients will decide upon the best treatment strategy for them, based on the information provided to them by their surgeon. This study offers additional results that can be used to facilitate treatment decisions in a patient-centred approach to clinical decision-making. There was a wide variation in QoL score throughout this cohort with scores ranging from as low as 98 to as high as 200. Because no clinical characteristics were found to be predictive of a patient’s QoL score, we would recommend a proactive approach towards QoL assessment in one’s VS patients.
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Conclusion The diagnosis of vestibular schwannoma has the potential to cause a substantial impact upon each patient’s quality of life and the present study demonstrates that this impact can occur regardless of the treatment strategy selected. The quality of life within this patient cohort was extremely variable in each management group, mirroring the
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heterogeneous natural history of this disease process. There was no difference in overall quality of life; however, those patients treated with microsurgery had significantly lower
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scores within the physical domain and were less likely to return to work.
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Figure 1
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Figure Legends
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Radar chart illustrating QoL scores in each domain as assessed by the FACT-Br. Values in each QoL domain are expressed as percentages of the total QoL score that could be achieved and the scale of the axis in each domain ranges from 60-100%. There are higher scores for the conservatively treated patients in the majority of QoL domains, however the surgery and radiosurgery cohorts have higher emotional and social QoL scores.
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Table 1 – Clinical Characteristics of the patient cohort
Mean Time Since Diagnosis (years)
57.2 (20-83) 24 (29%) 22 (27%) 20 (24%) 17 (20%)
60.3 (30-83) 12 (25%) 10 (20%) 15 (31%) 12 (24%)
4.9
55 (66%) 28 (34%)
Tumour Size (cm) <1.5 1.5-2.4 2.5-3.4 3.5-4.4 ≥4.5
41 (49%) 21 (25%) 7 (9%) 4 (5%) 9 (11%)
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Gender Female Male
Surgery
Radiotherapy
20 (24%)
14 (17%)
51.3 (20-70) 8 (40%) 6 (30%) 3 (15%) 3 (15%)
54.9 (35-73) 4 (29%) 6 (43%) 2 (14%) 2 (14%)
4.5
4.8
6.42
33 (67%) 16 (33%)
12 (60%) 8 (40%)
10 (71%) 4 (29%)
0 (0%) 4 (20%) 6 (30%) 2 (10%) 8 (40%)
5 (36%) 6 (43%) 1 (7%) 1 (7%) 1 (7%)
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49 (59%)
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Conservative
83
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Mean Age (range) <50 50-59 60-69 70+
All
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Patients (%)
36 (73%) 12 (24%) 0 (0%) 1 (2%) 0 (0%)
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Table 2 – Average QoL Scores Separated By Domain
Conservative
Surgery
Radiotherapy
p value†
Physical (0-28)
22.34
23.95
19.36
20.83
0.005
Social/Family (0-28)
23.94
24.57
23.07
22.99
0.42
Emotional (0-24)
17.22
17.40
16.14
18.21
0.54
Functional (0-28)
21.12
21.83
19.72
20.79
0.45
Brain Tumour Subscale Score (0-92)
68.83
70.80
65.51
66.97
0.35
General QoL Score (0-108)
84.75
87.50
79.85
82.46
0.18
Total (0-200)
153.35
158.29
144.64
148.76
0.17
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One Way ANOVA. QoL = Quality of Life.
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†
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All
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Table 3 – Odds Ratios and 95% Confidence Intervals for the association of various patient characteristics and a poor QoL outcome
1.35 1.37 1.65 1.02
(0.38-4.37) (0.27-6.79) (0.57-4.76) (0.78-1.34)
p value 0.64 0.69 0.34 0.86
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Size >2.5cm Surgical Management¥ Male Symptoms at Diagnosis* ¥
Multivariate Analysis‡ Odds Ratio (95% CI) p value
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Univariate Analysis Odds Ratio (95% CI)
1.25 2.12 1.00 1.68
(0.07-1.82) (0.12-38.0) (0.25-3.97) (0.99-3.18)
0.87 0.59 0.99 0.07
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Serial imaging as primary management strategy without surgical or radiotherapy intervention * Number of symptoms at the time of diagnosis as a result of one’s vestibular schwannoma ‡ Multivariate Analysis also controlling for age at diagnosis, age at time of the present study, treatment strategy, years since diagnosis, symptoms at time of the present study and number of comorbidities
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ACCEPTED MANUSCRIPT VS: Vestibular Schwannoma QoL: Quality of Life
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FACT-Br: Functional Assessment of Chronic Illness Therapy-Brain